The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat

Abstract

Objective: To investigate the effects of the antioxidant Tempol on prevention and reversal of adrenocorticotrophic hormone (ACTH)-induced hypertension in the rat, a model of hypertension characterized by nitric oxide deficiency. Methods: Male Sprague-Dawley rats (n = 10 in each group) were treated with either saline or ACTH (0.2 mg/kg per day, s.c.) for 12 days. Tempol (1 mmol/l in drinking water) treatment was started on either day 8 (T8) of ACTH or saline treatment (reversal study), or 4 days prior to ACTH or saline treatment (prevention study). Systolic blood pressure (SBP) was measured using tail-cuff sphygmomanometry. Plasma F2-isoprostanes, a marker of oxidative stress, were measured by gas chromatography-mass spectrometry. Results: ACTH increased SBP (mean ± SEM: 119 ± 5 to 147 ± 7 mmHg, P < 0.0005) and plasma F2-isoprostane concentration (8.4 ± 1.2 saline versus 12.9 ± 1.6 nmol/l ACTH, P < 0.05). Tempol alone did not alter SBP, but administration of Tempol on T8 reversed ACTH-induced hypertension (from 134 ± 4 T8 to 118 ± mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 ± 2 mmHg, P′ < 0.05). However, Tempol had no effect on F 2-isoprostane concentrations at the dose used in this study. Conclusions: ACTH-induced hypertension in the rat is associated with increased oxidative stress. Tempol treatment reversed, and pretreatment partially prevented ACTH-induced hypertension, independent of improvement in systemic oxidative stress.